Glioblastoma is a highly malignant brain tumor with a highly invasive phenotype and hence an unfavorable prognosis even in response to multidisciplinary treatment strategies. Ukrain, a semi-synthetic thiophosphoric acid derivative of the purified alkaloid chelidonine, has been used in the therapy of several solid tumors, but little is known about its effect on glioblastoma and, in general, about the molecular mechanisms responsible for its effects. We used RT-PCR, Western blot and SDS-zymography to investigate the effects of three doses of Ukrain (0.1, 1 and 10 μmol/l) on the expression of genes and proteins involved in the extracellular matrix remodeling associated with tumor invasion in human cultured glioblastoma cells treated for 24, 48 and 72 h. We analyzed the expression of matrix metalloproteinase-2 and -9, the main mediators of glioblastoma invasiveness, and secreted protein acidic and rich in cysteine (SPARC), involved in the regulation of cell–matrix interactions. There was a significant, dose-related decrease of glioblastoma cell proliferation and a tendency to downregulation of SPARC at the protein level 72 h after 10 μmol/l Ukrain, suggesting the drug may be a useful therapeutic tool for brain tumors.
Departments of aHuman Morphology–LITA Segrate
bBiology and Genetics, University of Milan, Milan, Italy
cUkrainian Anti-Cancer Institute, Vienna, Austria
Correspondence to N. Gagliano, University of Milan, Department of Human Morphology, Via Fratelli Cervi 93, Segrate, 20090 Milan, Italy
Tel: +39 02 50330462; fax: +39 02 50330452;
Received 15 September 2005 Accepted 14 October 2005